Conflicting reports of imprinting status of human GRB10 in developing brain: how reliable are somatic cell hybrids for predicting allelic origin of expression?
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Alleles↗
Biomedical subjects
M A Preece
Publications and source records attributed to M A Preece.
"Friendly fire" in medicine: hormones, homografts, and Creutzfeldt-Jakob disease.
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Causality↗
Is testosterone therapy for boys with constitutional delay of growth and puberty associated with impaired final height and suppression of the hypothalamo-pituitary-gonadal axis?
We report the treatment of 44 boys with constitutional delay of growth and puberty (CDGP) at a mean chronological age of 14.3 years (range, 12.4-17.1) and bone age of 12.1 years (range, 9.1-15.0). All were below the 3rd height percentile for chronological age. They received monthly intramuscular injections of depot testosterone esters (50 mg) for a mean period of 0.35 years (range, 0.25-0.5). Means (SD) height velocity was 4.5 (1.5) cm/year during a pretreatment period of 0.5 years. During a period of 0.9 years which included the period of treatment with depot testosterone, mean growth velocity increased to 8.8 (1.9) cm/year (P less than 0.001). In the initial 1.8 years following the cessation of treatment growth velocity was sustained at 7.0 (1.7) cm/year. Pretreatment height standard deviation score (SDS) for bone age was -0.89 and this gradually reduced over the next 1.5 years to a minimum of -1.48. Thereafter, height SDS for bone age gradually increased to attain a value of -1.2, 3 years after the commencement of therapy (P less than 0.02). The same pattern of an initial decrease, followed by an increase, in height prediction was also observed when TW2 height prediction was analysed. Sexual maturation progressed during treatment, with mean testicular volume increasing both during and after treatment, confirming the diagnosis of CDGP. The time interval for progress through puberty was shorter in boys with testosterone therapy than in the normal population. The mean duration of puberty was 2.2 years compared to 3.3 years in normal boys. We conclude that low-dose depot testosterone treatment is safe and effective for boys with CDGP.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Intensive enteral feeding in advanced cirrhosis: reversal of malnutrition without precipitation of hepatic encephalopathy.
Ten children with advanced cirrhosis and malnutrition (less than 90% weight for height) were fed for eight weeks with a nasogastric feed comprising whey protein (enriched with branched chain amino acids), fat as 34% medium chain and 66% long chain triglycerides, and glucose polymer. Six of the children were studied for an eight week control period before feeding. Weight, triceps skinfold thickness, mid-arm circumference, mid-arm muscle area, and fasting plasma ammonia and amino acid concentrations were measured before and after the control period and after the consequent feed period. Results showed that despite high energy and protein intakes the children remained malnourished over the control period. All anthropometric indices improved significantly during the feed period, and no child developed clinical encephalopathy. The feed period was associated with a small, and not clinically significant, increase in the plasma ammonia concentration, but no consistent trend in the plasma amino acid concentrations. Thus, in children with advanced hepatobiliary disease awaiting liver transplantation, enteral feeding improved nutritional status without adverse clinical or biochemical effects.
Amino Acids↗
Insulin and growth factors adaptation to normal puberty.
Insulin and IGF-1 production were measured throughout childhood and puberty and into adult life. Basal insulin and IGF-1 secretion increased during puberty, falling back to prepubertal levels in adulthood. However, fasting glucose levels remained constant, implying an increase in tissue resistance to insulin coinciding with puberty.
Adaptation, Physiological↗
The insulin-like growth factor (IGF)-binding proteins and IGF bioactivity in Laron-type dwarfism.
Laron-type dwarfism (LTD) is caused by a variable defect in the GH receptor gene and is, therefore, an ideal model to study the physiology of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in the complete absence of GH action. In this study we examined the overnight variation of the IGFs, IGFBPs, and IGF bioactivity in two prepubertal subjects with LTD. Subject 1 was a 14-yr-old female, 103 cm tall (-8.3 SD), and subject 2 was a 11.5-yr-old male, 103.6 cm tall (-5.9 SD). Both had serum IGF-I levels below 0.07 U/mL and low constant serum IGF-II levels overnight (185 +/- 10 and 232 +/- 8 micrograms/L), despite high serum GH levels [mean GH, 65 (32.5 micrograms/L) and 53 mU/L (26.5 micrograms/L)]. Serum IGFBP-1 levels increased overnight (from 24 and 22 micrograms/L at 2000 h to 83 and 110 micrograms/L at 0800 h) as serum insulin levels fell [from 19 (136 pmol/L) and 17 mU/L (122 pmol/L) at 2000 h to less than 2 (less than 14 pmol/L) and 5 mU/L (36 pmol/L) at 0800 h] in subjects 1 and 2, respectively. Serum IGFBP-2 levels remained constant overnight, as assessed on Western Ligand blotting and, despite the changes in IGFBP-1, remained the most prominent IGFBP throughout. On size separation, most of the IGF-II (greater than 60%) eluted with IGFBP-2 and the other low mol wt IGFBPs. Serum IGFBP-3 levels were reduced, and IGFBP-3 was not the major IGF carrier in LTD serum, in contrast to normal serum. An IGFBP-3-specific protease that was heat sensitive and cation dependent was identified as the cause of an apparent overnight rise of serum IGFBP-3 levels. No IGFBP-3 variation and no proteolytic activity was seen in normal serum or rapidly separated LTD plasma. Serum IGF bioactivity, measured in a porcine cartilage bioassay, was 0.18 and 0.55 U/mL in subjects 1 and 2; differences in bioactivity between subjects did not relate to serum IGF-II levels, but, rather, to differences in IGFBP-3 levels. Serum IGF bioactivity was not constant overnight and varied in a similar fashion in both subjects 1 and 2, with reduction in bioactivity between 0600-0800 h by 55% and 32%, suggesting the presence of inhibitory factors in the LTD serum; this decrease coincided with the rise in serum IGFBP-1 levels.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Growth hormone secretion in patients with Turner's syndrome as determined by time series analysis.
Twenty-four-hour growth hormone (GH) profiles in 26 girls with Turner's syndrome were compared with those of 26 normally growing short children and 24 slowly growing short children. All children were prepubertal and below 12 years of age. A subgroup of 13 girls was treated with ethinyl estradiol and a 24-h GH profile was reassessed. In an additional group of 45 girls with Turner's syndrome (aged 6.7-18.9 years) the effect of age, spontaneous breast development and ethinyl estradiol treatment was studied. The profiles were assessed by Fourier analysis. The oscillatory activity and the mean 24-h GH concentration were similar in children with Turner's syndrome and the normally growing short children, in contrast to lower levels in the slowly growing short children. The periodicity of GH secretion was similar in all groups. In the longitudinal study, ethinyl estradiol treatment resulted in a significant increase in pulse amplitude, but not in periodicity. In the cross-sectional study there was no significant difference between the subgroups of girls with either presence or absence of breast development or ethinyl estradiol treatment. GH secretion was not significantly related to age, height in standard deviation score or height velocity. These data imply that there is no abnormality in GH secretion in girls with Turner's syndrome.
Aging↗
The treatment of difficult atopic dermatitis in childhood with oral beclomethasone dipropionate.
Beclomethasone dipropionate (BDP) is a synthetic glucocorticoid with great topical potency. It has previously been demonstrated to be an effective treatment for childhood atopic dermatitis (AD) when given orally. We have monitored linear growth and adrenal function in a group of children treated with oral BDP for severe AD. Stable control of disease was achieved in 10/14 patients (mean dose: 1000 micrograms/day, range 800-1800). At this maintenance dose, there was evidence of deceleration of linear growth in 7/10 patients. There was no significant difference between pre-treatment 8 a.m. plasma cortisol levels and those on the maintenance dose. However, there was a reduction in 24-hour urinary cortisol excretion during maintenance treatment, although this did not reach statistical significance. We regard oral BDP as a useful treatment in widespread childhood atopic AD that has not responded adequately to topical therapy. However, it is mandatory that growth be monitored carefully during its use.
Beclomethasone↗
Growth hormone treatment in idiopathic short stature: a preliminary analysis of cardiovascular effects.
Growth hormone (GH) hypersecretion is associated with an increased incidence of hypertension and cardiac hypertrophy, resulting in excess cardiovascular morbidity and mortality. Abnormalities in the renin-angiotensin-aldosterone (RAA) system have been reported in acromegaly and in normal adults treated with recombinant human GH. The RAA system was investigated in prepubertal children with idiopathic short stature during treatment with recombinant human GH in doses up to 40 IU/m2/week. In addition, left ventricular size and function were assessed by serial echocardiography over an initial 12-month period. Modest and transient increases in blood pressure and body weight were observed during the first 7 days of GH treatment, but this was not accompanied by activation of the RAA system. Echocardiographic parameters of left ventricular size and function remained within the normal range for age and body size. Short-term GH treatment of idiopathic short stature was thus not associated with an increase in risk factors known to be associated with later cardiovascular morbidity. Longer follow-up studies will be required to confirm the safety of high-dose GH in this respect.
Blood Pressure↗
Auxological aspects of male and female puberty.
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Adolescent↗
Performance of proficiency survey samples in two immunoradiometric assays of human growth hormone and comparison with patients' samples.
The immunoradiometric assay (IRMA) used in our laboratory for the measurement of growth hormone (hGH; somatotropin) performed badly in the national proficiency survey program, the U.K. External Quality Assessment Scheme (EQAS). We compared our assay with another IRMA, which gave similar results for patients' samples and performed adequately in EQAS. The samples from EQAS are collected from patients with polycythemia and fall into two categories: those containing endogenous hGH and those supplemented with pituitary-derived hGH. Analysis of the two groups separately showed that the differences between the two IRMAS were in the measurement of the endogenous hormone. The reason for this appears to be a matrix effect related to the fact that the EQAS serum samples are collected from polycythemic patients.
Growth Hormone↗
Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom.
OBJECTIVE: To determine the cause of death and incidence of neoplasia in patients treated with human pituitary growth hormone. DESIGN: A long term cohort study established to receive details of death certification and tumour registrations through the Office of Population Censuses and Surveys and NHS central register. PATIENTS: All patients (1246 male, 662 female) treated for short stature with pituitary growth hormone under the Medical Research Council working party and health services human growth hormone committee. MAIN OUTCOME MEASURES: Death or development of neoplasia. RESULTS: 110 patients died (68 male, 42 female; aged 0.9-57 years) from 1972 to 1990. Fifty three death were from neoplasia responsible for growth hormone deficiency (27 craniopharyngioma, 24 other intracranial tumour, two leukaemia); two from histiocytosis X; and 13 from pituitary insufficiency. Six patients died of Creutzfeldt-Jakob disease, six of other neurological disorders, and eight of acute infection. Other deaths were apparently unrelated to growth hormone deficiency or its treatment. Seventeen tumours (in 16 patients) were identified during or after growth hormone treatment. Four were in patients with previous intracranial neoplasia and two were after cranial irradiation. Thirteen were intracranial, the others being Hodgkin's lymphoma, osteosarcoma, carcinoma of colon, and basal cell carcinoma. CONCLUSIONS: Recurrence or progression of intracranial tumours and potentially avoidable metabolic consequences of hypopituitarism were the main causes of death. Growth hormone treatment probably did not contribute to new tumour development. Creutzfeldt-Jakob disease after pituitary growth hormone treatment continues to occur in the United Kingdom. This cohort must remain under long term review.
Adolescent↗
Possible deleterious effect of L-carnitine supplementation in a patient with mild multiple acyl-CoA dehydrogenation deficiency (ethylmalonic-adipic aciduria).
A patient with riboflavin-responsive mild multiple acyl-CoA dehydrogenation deficiency of the ethylmalonic--adipic aciduria type experienced a recurrence of spontaneous hypoglycaemic episodes whilst being given supplementary L-carnitine. This phenomenon is explicable in terms of the known biochemical features of this condition and suggests caution in the carnitine supplementation of patients with defective oxidation of medium- or short-chain fatty acyl-CoA esters. This patient excreted excessive phenylpropionylglycine after an oral phenylpropionic acid load. Thus the phenylpropionic acid loading test is not completely specific for primary medium-chain acyl-CoA dehydrogenase deficiency as has been supposed.
Acyl-CoA Dehydrogenases↗
Pulsatile growth hormone secretion in peripubertal patients with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure.
The pubertal growth spurt has been associated with changes of physiologic pulsatile growth hormone (GH) secretion, and abnormalities of the central regulation of GH release have been found by pharmacologic testing in patients with chronic renal failure. To assess the characteristics of GH pulsatility in chronic renal failure and their relationship to pubertal growth, we studied spontaneous nighttime GH plasma profiles in 80 patients (61 boys) aged 10 to 20 years receiving conservative treatment (n = 29) or dialysis (n = 18) or after renal transplantation (n = 33). Tanner genital stages 1 to 4 in boys and breast stages 1 to 3 in girls were represented. Growth hormone pulse analysis was performed by the PULSAR algorithm. Growth hormone concentration profiles were pulsatile in each patient. Growth hormone mean and baseline levels and pulse amplitudes were higher in patients receiving conservative or dialysis treatment than in patients who had undergone renal transplantation. Peak frequency was similar in all treatment groups in boys but higher in girls who had undergone transplantation than in girls receiving conservative or dialysis treatment. Growth hormone peak amplitude and mean levels were lowest in patients in late puberty. The physiologic elevation of GH amplitudes around midpuberty was observed in boys receiving conservative and dialysis treatment but not after transplantation. Growth hormone mean and baseline levels were positively correlated with plasma androgen levels in boys. Growth hormone peak amplitude was correlated with 6-month height velocity after transplantation but not in patients receiving conservative treatment or dialysis. A strong inverse relationship was observed between GH peak amplitude and corticosteroid dosage in patients undergoing transplantation. The lack of relationship between circulating GH levels and growth in patients receiving conservative or dialysis treatment is compatible with end-organ hyporesponsiveness to GH. Pubertal growth failure despite successful transplantation appears to be related to steroid-induced GH hyposecretion.
Adolescent↗
Modern management of growth problems in skeletal dysplasias.
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Bone Diseases, Developmental↗
Clinical spectrum of the syndrome of growth hormone insensitivity. Advisory Committee on Growth Hormone Insensitivity.
A survey of 46 patients with suspected growth hormone (GH) insensitivity is presented. Clinical details and plasma samples from these patients were analysed centrally. A diagnostic score based on basal levels of GH and insulin-like growth factor I (IGF-I), IGF-I response to GH (0.1 U/kg daily for 4 days) and height SDS was determined for all patients to identify those with GH insensitivity. A total of 29 such patients was identified (14 males and 15 females; age range, 3.2-22.6 years). Their mean height SDS was -6.0 (range, -8.9 to -2.6), mean weight SDS was -2.9 (range, -5.2 to 1.2). Pubertal development was delayed in three out of three boys and two out of six girls of pubertal age. Their basal GH level was 32.4 mU/l (range, 0.8-158.2 mU/l) and mean basal IGF-I level was 33.6 ng/ml (range, 20-97 ng/ml). None of the 29 patients showed a significant serum IGF-I response to injections of GH.
Adolescent↗
Reproducibility of 24-hour serum growth hormone profiles in man.
OBJECTIVE: To study the reproducibility of 24-h serum growth hormone (GH) concentration profiles in adults. DESIGN: 24-h serum GH concentrations were constructed by drawing blood samples at 20-min intervals. Four study occasions over a period of 1 year were chosen to assess the reproducibility. SUBJECTS: Six healthy adult male volunteers of normal height and weight and aged between 20 and 22 years. MEASURES: The resulting GH data arrays were analysed by Fourier transformation. Between and within individual variations were calculated and expressed in terms of coefficients of variation and data plotted to show variations between groups and individuals. RESULTS: The frequency component of GH secretion occurred with a dominant periodicity of between 160 and 240 min. Precise estimates of spectral power (strength of oscillatory activity) and period were obtained for group data, but such estimates cannot be inferred from a single profile. There was no significant difference in 24-h mean serum GH concentration over the year of study: occasion 1 (February) mean 2.0 mU/l (SD 0.5); occasion 2 (March) mean 3.7 mU/l (SD 2.8); occasion 3 (July) mean 2.7 mU/l (SD 1.4); occasion 4 (February) 2.5 mU/l (SD 1.5) (mean within individual coefficient of variation 35%, range 9-58). The concentrations of factors known to influence GH synthesis and secretion, insulin-like growth factor I, thyroxine, testosterone and oestradiol, varied little over the year of study. CONCLUSIONS: These data demonstrate that group data are reproducible in terms of oscillatory activity and the amount of GH secreted and that 24-h GH profiles should be used predominantly for analysing group data. The variability between individual profiles limits their value in the investigation of children with growth failure and suspected GH insufficiency.
Adult↗
Changes in skeletal muscle and body composition after discontinuation of growth hormone treatment in growth hormone deficient young adults.
OBJECTIVES: The aim of this study was to determine whether there are any changes in skeletal muscle strength and size and body composition following growth hormone (GH) withdrawal in GH deficient young adults. DESIGN: A longitudinal, 1-year, open, uncontrolled study of the changes in skeletal muscle and body composition following GH withdrawal was performed. Endocrine status was reassessed at the end of the study period during an insulin tolerance test. Some measurements were repeated after 2 years of treatment. PATIENTS: Twelve (11 male, one female; age range 14-21) patients who had been diagnosed during childhood as growth hormone deficient took part in the study. Four of the 12 patients were found to have a normal GH response on retesting at the end of the study and their results were analysed as a separate group. MEASUREMENTS: Quadriceps and forearm flexor maximum voluntary isometric strength, body fat content and serum IGF-1 were measured at 3-monthly intervals over 1 year. Every 6 months muscle size was measured from computerized tomography scans and fibre area from quadriceps needle biopsy samples. RESULTS: For the growth hormone deficient group the 12 month quadriceps strength, size and fibre areas were 94.0% +/- 8.5 (mean +/- SD), 94.5% +/- 6.3 and 85.6% +/- 17.7 respectively of control (baseline) values. Forearm flexor strength and size were 101.4% +/- 7.9 and 92.0% +/- 9.2 of control. Body fat percentage had increased from 19.5% +/- 8.6 to 24.1% +/- 9.5. No change was seen in the non-growth hormone deficient group. CONCLUSIONS: Although the changes measured were relatively small they suggest a role for GH in the maintenance of muscle integrity and body composition in the young adult with growth hormone deficiency.
Adolescent↗